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Truth Behind Atherosclerosis

Truth Behind Atherosclerosis

What is really to blame for heart disease?

Well, it’s certainly not cholesterol that causes atherosclerosis. Most researchers understand that by now. But most of the public and general practitioners do not. We still look at the same old risk factors, like LDL cholesterol. But that cholesterol is not inherently bad – it has very specific purpose.

If you are interested in the story of what cholesterol is, check out this post that explains it. All the lipoproteins that carry cholesterol around to cells are there to also deliver fat and phospholipids. You can think of cholesterol just hitching a ride with the triglycerides. They also are sometimes sent out for other purposes, like repair.

But certainly there is a correlation with cholesterol and heart disease. As we all know, researchers found that plaque of people affected by atherscolerosis contains cholesterol and other fatty substances.[1]

But this week’s research paper suggests the reason for all the cholesterol in the plaque is that it has come to repair lesions. Also, a vitamin C deficiency has lead to a weakening of the extracellular matrix, thus making it more susceptible to cholesterol and lipids coming into the vascular wall. The cholesterol comes to repair what vitamin C normally does with the collagen matrix, but it can get stuck, oxidized, and then eaten by macrophages to form foam cells.[2]

Vitamin C for athersclerosisSummary

We are discussing an article on the different theories of atherosclerosis from history and how they stand up to scrutiny.[2] [Click here for the research file.]

Wong AP, Mohamed AL, Niedzwiecki A. (2016). Atherosclerosis and the Cholesterol Theory: A Reappraisal. World Journal of Cardiovascular Diseases 6: 391-409.


  • The theories of heart disease have changed form over time. Beliefs went from the lipid hypothesis (cholesterol causes disease) to the oxidized LDL cholesterol hypothesis to the respond-to-injury hypothesis.
    • None of these are fully understood, and we still more RCTs for confirmation.
  • The weakening of the collagen matrix is the causes of heart disease. It then requires repair teams of LDL and lipoprotein(a) to come in.
  • Vitamin C helps keep the extracellular matrix strong by synthesizing collagen. A deficiency will lead to the weakening of the vascular walls.
  • Thus adequate vitamin C helps to prevent and even reverse atherosclerosis. Many trials on mice have reported this.
  • Humans don’t make vitamin C endogenously. Though our body makes lipoprotein(a) endogenously, and it takes on the repair roles when vitamin C is not there. So having enough vitamin C will lead to lower levels of this “sticky” lipoprotein.

Introduction

What is atherosclerosis? As the researchers define it, “Atherosclerosis is [a] condition where arteries become narrowed and hardened due to plaque buildup around the artery wall. Over time, this occlusion limits flow of oxygen-rich blood to the heart. Atherosclerosis is the precedent to coronary heart disease (CHD).”[2] Wow, that doesn’t sound very good. Yes, atherosclerosis is that condition where you have nasty plaque clogging your arteries.

But how are we supposed to prevent it? That is the big question that researchers have been dealing with for decades. The only way we can figure out how to avoid it is if we understand the true root causes. From that need, doctors and researchers have come out with theories and hypotheses to explain the gross phenomenon.

First there was the lipid hypothesis, which stated that cholesterol is the causal factor for heart disease. Most doctors still run with that hypothesis. There has been a lot of debate among professionals about the difference between serum fat and dietary fat. Serum fat is bad for you, but does dietary fat necessarily lead to that? Nope. A ketogenic diet will raise your cholesterol, but it lowers serum triglycerides.[3] That’s what matters. It’s because you become a fat burning machine.

Then came about the more “modern” theories like the respond-to-injury-theory, the oxidized LDL theory, and the monoclonal theory. The first one says cholesterol might be there to repair problems. The second says that it isn’t LDL that is the problem, it is its oxidized form that is. And lastly, the monoclonal theory states that heart disease originates out of one pathogenic cell that reproduces and eventually causes an entire artery to be messed up. But this paper was more about the debunking of the cholesterol theory, so we don’t go into too much detail about these other ones. We found that a blend of these theories cause heart disease.

 

History of the causes of atherosclerosis

Table of the progression of understanding atherosclerosis

The researchers go through a brief history of the hypotheses behind heart disease. How did they start and how have they changed? The issue of heart disease and cholesterol came about from autopsy studies. Some scientists discovered that the arteries of people who died of heart complications had a fatty substance that clogged the blood flow. The first time it was related back to cholesterol was when Dr. Anichkov (1913) saw that feeding cholesterol dissolved in sunflower oil induced lesions in the arterial wall.[2]

First of all, sunflower oil is made up of mostly polyunsaturated fats (linoleic acid). We steer clear of that in a ketogenic diet. So, I don’t even doubt Anichkov is wrong. But anyway, this started people down the path to check out cholesterol. Then came Ancel Keys. He is the guy mostly responsible for the dietary changes we have now. He reported that countries with a higher fat intake had a higher rate of heart disease. But that was all just epidemiological studies – noting randomized or controlled.

Another meta-analysis showed that all of the guidelines we have today are not based on actual randomized controlled trials (RCTs). The RCTs that were available actually showed no correlation between saturated fat intake and heart disease.[4] Isn’t that just disturbing? Bastards.

But then after all of that came a very interesting hypothesis: that oxidized LDL cholesterol was the problem, not simply LDL. When LDL is oxidized, it then becomes consumed by macrophages, which are there to clean up harmful substrates. When the macrophages do that, they become “foam cells” which are early culprits of atherolsclerosis.[5][6][7] Studies show mixed results with antioxidants and atherosclerosis – so this theory still has a lot of unanswered questions. But it is still strong.

Link between vitamin C and heart disease

Then we come to the main crux of the article: vitamin C. This is actually really cool because I hadn’t known that vitamin C plays such an important role in heart health. But it does. Research claims that a deficiency of vitamin C will lead to the “capillary fragility.” This means that without vitamin C, your endothelial walls become weaker. Interesting… (All of this makes sense when you understand vitamin C’s role in biology. We will get into that in a sec.)

Also, they talk about how atherosclerosis doesn’t occur everywhere in blood vessels – just those places that experience high mechanical stress (like the arteries…). That implies that it is not just having cholesterol around that is the problem. The stress on specific parts of your cardiovascular system that is to blame. This concept in combination with the weakening of your capillary walls can explain one of the problems causing atherosclerosis.

One more point about vitamin C before moving on. People who are given high doses of vitamin C also have less cholesterol in their system. We do not think that is a good thing all on its own, but it can explain the important relationship between cholesterol and vitamin C. Let’s take a look.

Lipoprotein(a) & apo(a)

General lipoprotein structure


LDL has been deemed the “bad cholesterol” because it associates well with heart disease. We debunk this idea in another post, but for now, let’s shift focus to another (similar) carrier, lipoprotein(a). Lp(a) is very similar in structure to LDL, but it has apolipoprotein(a), which LDL does not have. There have been studies that suggest a positive correlation between serum Lp(a) and heart disease.
[8] It was even detected in the arterial wall of heart failure patients.[9]

But this also leads back to the respond-to-injury theory because apo(a) is involved in tissue repair processes.[10] So this means that possibly Lp(a) is strongly correlated with atherosclerosis because it is there to start the repair. Perhaps the repair needs to happen because of the lack of vitamin C to make a strong extracellular matrix. That’s what these researchers propose.

They even talk about how Lp(a) is a “surrogate” for vitamin C. That means when not enough vitamin C is around, your body will create more Lp(a) to do its job. And actually researchers have shown this to be true. The animal species that have high levels of Lp(a) (primates and guinea pigs) are the same ones that cannot produce vitamin C endogenously.[11]

Let’s try to understand this one point. Vitamin C plays a critical role in the extracellular matrix and collagen production. Lp(a) plays a critical role in extracellular repair. That might be why having a high amount of vitamin C will decrease the amount of Lp(a) floating around.

Breakdown of the extracellular matrix

The researchers explain that a reduction in vitamin C will actually stimulate atherosclerosis. As stated above, vitamin C has a very important role in helping the arterial walls maintain integrity. Vitamin C affects synthesis of collagen protein, which is the fibrous material that holds cells together. This is a major part of the extracellular matrix. Without collagen, the cells start to fall apart and form gaps.

Then the job of apo(a) is to come and repair that matrix. It wants to make your arterial walls stronger, but it gets stuck in it. Other proteins which are synthesized by vitamin C are direct competitors with Lp(a). That means when these proteins are not available, the Lp(a) comes to do the job, but it can’t do it as well. It just ends up piling on itself. Then perhaps it oxidizes and turns macrophages into foam cells which also pile up.

(A ketogenic diet will lead to less oxidative species, so this doesn’t become as much of a problem. Check out our post on that topic here.)

Vitamin C is the answer

From all of this, the researchers propose that incorporating enough vitamin C will reduce the chance of atherosclerosis. And actually studies on mice show that vitamin C will reduce the amount of Lp(a) in the blood, and will thus lead to less atherosclerosis.[11] They suggest that “CHD is an early form of the vitamin C deficiency disease, scurvy leading to vascular deposition of Lp(a).” Amazing.

Vitamin C for heart health!

They conclude with 3 questions that are made to get us thinking about current understandings of heart disease:

1) Why is cholesterol only in the arteries and not the veins even though cholesterol flows through the entire vascular system?

2) Why does sclerosis only occur in the length of the coronary arteries (a few inches long) when the vascular system can stretch to about 60 miles?

3) Why is atherosclerosis pretty much unique to humans (and other non-vitamin C producing animals) while not occurring in a majority of other animal species?

These are hard questions to answer, but I think the clear plan of action to stop heart disease becomes a little more clear after reading this article. Apparently vitamin C is pretty important. Who knew?

Summary

  • The theories of heart disease have changed form over time. Beliefs went from the lipid hypothesis (cholesterol causes disease) to the oxidized LDL cholesterol hypothesis to the respond-to-injury hypothesis.
    • None of these are fully understood, and we still more RCTs for confirmation.
  • The weakening of the collagen matrix is the causes of heart disease. It then requires repair teams of LDL and lipoprotein(a) to come in.
  • Vitamin C helps keep the extracellular matrix strong by synthesizing collagen. A deficiency will lead to the weakening of the vascular walls.
  • Thus, adequate vitamin C helps to prevent and even reverse atherosclerosis. Many trials on mice have reported this.
  • Humans don’t make vitamin C endogenously. Though our body makes lipoprotein(a) endogenously, and it takes on the repair roles when vitamin C is not there. So having enough vitamin C will lead to lower levels of this “sticky” lipoprotein.

References:

[1] Virmani R, Kolodgie FD, Burke AP, Finn AV, Gold HK, Tulenko TN, Wrenn SP, Narula J. (2005). Atherosclerotic Plaque Progression and Vulnerability to Rupture. Arteriosclerosis, Thrombosis, and Vascular Biology 25(10): 2054-2061.

[2] Wong AP, Mohamed AL, Niedzwiecki A. (2016). Atherosclerosis and the Cholesterol Theory: A Reappraisal. World Journal of Cardiovascular Diseases 6: 391-409.

[3] Yancy WS, Foy M, Chalecki AM, Vernon MC, Westman EC. (2005). A low-carbohydrate, ketogenic diet to treat type 2 diabetesNutrition & Metabolism 2: 34.

[4] Harcombe Z, Baker JS, Cooper SM, Daview B, Sculthorpe N, DiNicolantonio J, Grace F. (2015). Evidence from randomised controlled trials did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review and meta-analysis. Open Heart 

[5] Henriksen T, Mahoney EM, Steinberg D. (1981). Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: recognition by receptors for acetylated low density lipoproteins. Proceedings of the National Academy of Sciences of the United States of America 75(10): 6499-6503.

[6] Hessler JR, Morel DW, Lewis LJ, Chisolm GM. (1983). Lipoprotein oxidation and lipoprotein-induced cytotoxicityArteriosclerosis, Thrombosis, and Vascular Biology 3(3): 215-222.

[7] Steinbrecher UP, Parthasarathy S, Leake DS, Witztum JL, Steinberg D. (1984). Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipidsProceedings of the National Academy of Sciences of the United States of America 81(12): 3883-3887.

[8] Armstrong VW, Cremer P, Eberle E, Manke A, Schulze F, Wieland H, Kreuzer H, Seidel D. (1986). The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis: Dependence on serum LDL levels. Atherosclerosis 62(3): 249-257.

[9] Walton KW, Hitchens J, Magnani HN, Khan M. (1974). A study of methods of identification and estimation of LP(a) lipoprotein and of its significance in health, hyperlipidaemia and atherosclerosis. Atherosclerosis 20(2): 323-346.

[10] Stenman S, von Smitten K, Vaheri A. (1980). Fibronectin and Atherosclerosis. Journal of Internal Medicine 208(S642): 165-170.

[11] Cha J, Niedzwiecki A, Rath M. (2015). Hypoascorbemia induces atherosclerosis and vascular deposition of lipoprotein(a) in transgenic mice. The American Journal of Cardiovascular Disease 5(1): 53-62.

 

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